U.S. patent number 5,555,885 [Application Number 08/093,208] was granted by the patent office on 1996-09-17 for examination of breast tissue using time-resolved spectroscopy.
This patent grant is currently assigned to Non-Invasive Technology, Inc.. Invention is credited to Britton Chance.
United States Patent |
5,555,885 |
Chance |
September 17, 1996 |
**Please see images for:
( Certificate of Correction ) ** |
Examination of breast tissue using time-resolved spectroscopy
Abstract
A method of breast tissue examination using time-resolved
spectroscopy includes the following steps. A support that includes
an input port and an output port separated by a selected distance
is positioned relative to the examined breast. Locations of the
input and output ports are selected to examine a tissue region of
the breast. Light pulses of a selected wavelength and duration less
than a nanosecond are introduced into the breast tissue at the
input port and detected over time at the detection port. Signals
corresponding to photons of detected modified pulses are
accumulated over time. Values of a scattering coefficient or an
absorption coefficient of the examined breast tissue are calculated
based on the shape of the modified pulses. The examined breast
tissue is characterized based on the values of the scattering
coefficient or the absorption coefficient. Absorbing or fluorescing
contrast agents may be introduced into the examined tissue. This
method may be used in conjunction with x-ray mammography, needle
localization procedure or MRI mammography.
Inventors: |
Chance; Britton (Marathon,
FL) |
Assignee: |
Non-Invasive Technology, Inc.
(Philadelphia, PA)
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Family
ID: |
22237753 |
Appl.
No.: |
08/093,208 |
Filed: |
July 16, 1993 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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40168 |
Mar 30, 1993 |
5386827 |
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876364 |
Apr 30, 1992 |
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287847 |
Dec 21, 1988 |
5119815 |
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Current U.S.
Class: |
600/431; 600/475;
600/477 |
Current CPC
Class: |
A61B
5/0091 (20130101); A61B 5/14552 (20130101); A61B
5/4312 (20130101); G01J 3/2889 (20130101); G01N
21/49 (20130101); G01N 21/59 (20130101); G01N
2021/1791 (20130101); G01N 2021/4797 (20130101) |
Current International
Class: |
A61B
5/00 (20060101); G01N 21/47 (20060101); G01N
21/49 (20060101); G01J 3/28 (20060101); G01N
21/59 (20060101); A61B 006/00 () |
Field of
Search: |
;128/664-665,633,634,654 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Cardio-Green.RTM. (CG.RTM.), HW&D Brand of Sterile Indocyanine
Green, USP (1981). .
O'Leary, Boas, Chance, Yodh, "Refraction of Diffuse Photon Density
Waves," Phys. Rev. Lett. 69:2658 (1992). .
Boas, O'Leary, Chance, Yodh, "Scattering and wavelength
transduction of diffuse photon density waves," Physical Review E
47:2999-3002 (May, 1993). .
Bonner et al., "A Random Walk Theory of Time-Resolved Optical
Absorption Spectroscopy in Tissue", Photon Migration in Tissues ed.
Britton Chance, 1989, Plenum Press. .
Chance et al., "Comparison of time-resolved and -unresolved
measurements of deoxyhemoglobin in brain", Proc. Natl. Acad. Sci.
USA 85:4971-4975 (1988). .
Chance, "Time-Resolved Spectroscopy of Hemoglobin and Myoglobin in
Resting and Ischemic Muscle", Analytical Biochemistry 174:698-707
(1988). .
Kang et al., "Breast Tumor Characterization Using NIR Spectroscopy"
Abstract Paper 1888-55, Biomedical Optics 1993, Jan. 16-22. .
Kang et al., "Breast Tumor Characterization Using Near-Infra-Red
Spectroscopy", SPIE Proceedings, 1888 Photon Migration and Imaging
in Random Media and Tissues, ed. Britton Chance. .
Lakowicz, "Gigahertz Frequency-Domain Fluorometry: Resolution of
Complex Intensity Decays, Picosecond Processes and Future
Developments", Photon Migration in Tissues, pp. 169-186 (1989),
Plenum Press..
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Primary Examiner: Smith; Ruth S.
Attorney, Agent or Firm: Fish & Richardson P.C.
Government Interests
STATEMENT AS TO FEDERALLY SPONSORED RESEARCH
This invention was made in the course of work supported in part by
the U.S. Government, which has certain rights in the invention.
Parent Case Text
CROSS REFERENCE TO RELATED APPLICATIONS
This application is a continuation-in-part of a U.S. patent
application Ser. No. 08/040,168, filed Mar. 30, 1993 entitled
"QUANTITATIVE AND QUALITATIVE IN VIVO TISSUE EXAMINATION USING TIME
RESOLVED SPECTROSCOPY" now U.S. Pat. No. 5,386,827 and a
continuation-in-part of U.S. patent application Ser. No. 07/876,364
filed Apr. 30, 1992 now abandoned, which is a continuation of U.S.
patent application Ser. No. 07/287,847 filed Dec. 2, 1988 now U.S.
Pat. No. 5,119,815, all of which are incorporated by reference as
if set forth in their entireties herein.
Claims
I claim:
1. A method for examination of breast tissue of a female subject
using pulses of light of a selected wavelength, said method
comprising the steps of:
(a) providing a support, positioned relative to the examined
breast, comprising a set of input ports and a set of output ports
separated by a selected distance, each said input port constructed
to define an irradiation location of said breast, each said output
port constructed to define a detection location of said breast,
(b) selecting locations of said input and output ports to examine a
tissue region of the breast,
(c) introducing into the breast tissue, at said selected input
port, pulses of light of a selected wavelength in the visible or
infra-red range, said pulses having duration of less than about a
nanosecond,
(d) detecting over time, at said selected detection port, photons
of modified pulses that have migrated in the breast tissue,
(e) integrating said photons over at least two selected time
intervals separately spaced over the arrival time of said modified
pulses,
(f) calculating a value of an absorption coefficient (.mu..sub.a)
of the examined breast tissue based on the number of photons
integrated over each time interval, and
(g) characterizing the examined breast tissue based on said value
of the absorption coefficient.
2. The method of claim 1 wherein said (e) and (f) steps further
comprise:
integrating said photons over other selected time intervals
separately spaced over the arrival time of said modified
pulses,
determining the time delay (t.sub.max) between a time when a pulse
is introduced and a time at which the corresponding modified pulse
has the maximum value, based on the number of photons integrated
over said time intervals, and
calculating a value of a scattering coefficient (.mu..sub.s) of the
examined breast tissue by employing said absorption coefficient and
said time delay.
3. The method of claim 2 further comprising the steps of:
(h) moving said input port and said output port to a different
location to examine a second tissue region of the breast,
(i) repeating steps (c) through (f) to determine a value of the
scattering coefficient of said second tissue region, and
(j) characterizing the examined breast tissue based on said values
of the scattering coefficient.
4. The method of claim 3 wherein said characterizing step further
includes comparing said calculated values of the scattering
coefficient with a selected value of the scattering
coefficient.
5. The method of claim 4 wherein said selected value of the
scattering coefficient is one value selected from the group
consisting of: a value of normal breast tissue of the examined
breast, a value of normal breast tissue of the contralateral breast
and a value of a homogenous breast tumor.
6. The method of claim 1 or 2 comprising an initial step of
injecting into the blood stream of said subject a contrast agent
exhibiting known optical properties at said selected
wavelength.
7. The method of claim 6 wherein said injecting step includes first
selecting a contrast agent from the group consisting of: a
cardio-green contrast agent, a indocyanine-green contrast agent, a
rare earth element based contrast agent, and a fluorescent contrast
agent.
8. The method of claim 6 wherein said injecting step includes first
selecting a contrast agent that is preferentially absorbed by a
tissue mass.
9. The method of claim 2 wherein said characterizing step further
includes comparing said calculated value of the scattering
coefficient to a selected value of the scattering coefficient.
10. The method of claim 9 wherein, upon determining that said
calculated value matches a selected value of the scattering
coefficient of abnormal tissue, said method further comprising the
steps of:
(h) selecting another location of said input port and said output
port to define a second tissue region proximate to said measured
region,
(i) repeating steps (c) through (f) to determine a value of the
scattering coefficient of the second tissue region, and
(j) localizing said measured region or said abnormal breast tissue
value by comparing calculated values of the scattering coefficient
of different selected tissue regions.
11. The method of claim 10 further comprising determining type of
the abnormal tissue by comparing said calculated values of the
scattering coefficient of said localized tissue to a value of the
scattering coefficient of a selected tissue mass.
12. The method of claim 11 wherein said tissue mass is selected
from the group consisting of: carcinoma, fibroadenoma and
fibrocystic tissue.
13. The method of claim 10 wherein said localization step includes
determining the size of said abnormal tissue region.
14. The method of claim 10 wherein said localization step includes
determining the location of said abnormal tissue region.
15. The method of claim 9 wherein, upon determining that said
calculated value matches a selected value of the scattering
coefficient of abnormal tissue, said method further comprising the
steps of:
(h) injecting into the blood stream of said subject a contrast
agent exhibiting known optical properties at said selected
wavelength,
(i) repeating steps (c) through (f) to determine values of the
scattering coefficient of tissue with said contrast agent, and
(j) characterizing said abnormal tissue by comparing said
calculated value of the scattering coefficient of the examined
tissue with said contrast agent with selected values of the
scattering coefficient.
16. The method of claim 15 further comprising the steps of:
(k) selecting another location of said input port and said output
port to define a second tissue region proximate to said examined
tissue region,
(l) repeating steps (c) through (f) to determine a value of the
scattering coefficient of said second tissue region,
(m) localizing said abnormal breast tissue by comparing said
determined value of the scattering coefficient of different
selected tissue regions.
17. The method of claim 15 wherein said injecting step includes
first selecting a contrast agent that is preferentially absorbed by
abnormal tissue.
18. The method of claim 15 wherein said injecting step includes
first selecting a contrast agent that fluoresces when irradiated,
and said detecting step includes detecting fluorescent radiation
emitted from said contrast agent.
19. The method of claim 15 wherein said injecting step includes
first selecting a contrast agent from the group consisting of: a
cardio-green contrast agent, a indocyanine-green contrast agent, a
rare earth element based contrast agent, and a fluorescent contrast
agent.
20. The method of claim 1 further comprising the steps of:
(h) moving said input port and said output port to a different
location to examine a second tissue region of the breast,
(i) repeating steps (c) through (f) to determine a value of the
absorption coefficient of said second tissue region, and
(j) characterizing the examined breast tissue based on said values
of the absorption coefficient.
21. The method of claim 20 wherein said characterizing step further
includes comparing said calculated values of the absorption
coefficient with a selected value of the absorption
coefficient.
22. The method of claim 21 wherein said selected value of the
absorption coefficient is one value selected from the group
consisting of: a value of normal breast tissue of the examined
breast, a value of normal breast tissue of the contralateral breast
and a value of a homogenous breast tumor.
23. The method of claim 1 wherein said characterizing step further
includes comparing said calculated value of the absorption
coefficient to a selected value of the absorption coefficient.
24. The method of claim 23 wherein, upon determining that said
calculated value matches a selected value of the absorption
coefficient of abnormal tissue, said method further comprising the
steps of:
(h) selecting another location of said input port and said output
port to define a second tissue region proximate to said measured
region,
(i) repeating steps (c) through (f) to determine a value of the
absorption coefficient of the second tissue region, and
(j) localizing said measured region of said abnormal breast tissue
value by comparing calculated values of the absorption coefficient
of different selected tissue regions.
25. The method of claim 24 further comprising determining type of
the abnormal tissue by comparing said calculated values of the
absorption coefficient of said localized tissue to a value the
absorption coefficient of a selected tissue mass.
26. The method of claim 25 wherein said tissue mass is selected
from the group consisting of: carcinoma, fibroadenoma and
fibrocystic tissue.
27. The method of claim 24 wherein said localization step includes
determining the size of said abnormal tissue region.
28. The method of claim 24 wherein said localization step includes
determining the location of said abnormal tissue region.
29. The method of claim 23 wherein, upon determining that said
calculated value matches a selected value of the absorption
coefficient of abnormal tissue, said method further comprising the
steps of:
(h) injecting into the blood stream of said subject a contrast
agent exhibiting known optical properties at said selected
wavelength,
(i) repeating steps (c) through (f) to determine values of the
absorption coefficient of tissue with said contrast agent, and
(j) characterizing said abnormal tissue by comparing said
calculated values of the absorption coefficient of the examined
tissue with said contrast agent with selected values of the
absorption coefficient.
30. The method of claim 29 further comprising the steps of:
(k) selecting another location of said input port and said output
port to define a second tissue region proximate to said examined
tissue region,
(l) repeating steps (c) through (f) to determine values of the
absorption coefficient of said second tissue region,
(m) localizing said abnormal breast tissue by comparing said
determined values of the absorption coefficient of different
selected tissue regions.
31. The method of claim 29 wherein said injecting step includes
first selecting a contrast agent that is preferentially absorbed by
abnormal tissue.
32. The method of claim 29 wherein said injecting step includes
first selecting a contrast agent that fluoresces when irradiated,
and said detecting step includes detecting fluorescent radiation
emitted from said contrast agent.
33. The method of claim 29 wherein said injecting step includes
first selecting a contrast agent from the group consisting of: a
cardio-green contrast agent, a indocyanine-green contrast agent, a
rare earth element based contrast agent, and a fluorescent contrast
agent.
34. A system for in vivo examination of breast tissue of a female
subject, comprising:
a light source constructed to generate pulses of light of a
selected wavelength in the visible or infra-red range, said pulses
having duration of less than about a nanosecond,
a support, positionable relative to said breast tissue, comprising
a set of input ports and a set of output ports separated by a
selected distance,
each said input port constructed to define an irradiation location
of said breast, one of said input ports optically connected to said
source and constructed to introduce into the breast tissue said
generated pulses of light of said selected wavelength,
each said output port constructed to define a detection location of
said breast,
a detector, optically connected to one of said output ports,
constructed to detect over time photons of modified pulses that
have migrated in said breast tissue to said output port and produce
corresponding electrical signals,
a gated integrator and an integrator timing control constructed to
receive said signals and to integrate said detected photons over at
least two selected time intervals separately spaced over the
arrival time of said modified pulses, and
a processor connected to said integrator and constructed to
calculate a value of an absorption coefficient (.mu..sub.a) of the
examined breast tissue based on the number of photons integrated
over each time interval and determine a physiological property of
the examined breast tissue based on said absorption
coefficient.
35. The system of claim 34 wherein said gated integrator, said
integrator timing control, and said processor are further
constructed to determine the delay time (t.sub.max) between a time
when a pulse is introduced and a time at which the corresponding
modified pulse has the maximum value, and said processor being
further programmed to determine the effective scattering
coefficient (1-g).multidot..mu..sub.s of the examined tissue.
36. The system of claim 34 or 35 wherein said support is
constructed to enable accurate selection of a region of a breast
based on a relative geometry of said irradiation location and said
detection location.
37. The system of claim 34 or 35 wherein said support is
constructed with said input port and said output port adapted to
touch the skin of said examined breast.
38. The system of claim 37 wherein said support includes a pliable
material.
39. The system of claim 37 wherein said support includes a rigid
material of a selected shape.
40. The system of claim 39 or 35 further including an exogenous
contrast agent of known optical properties, said light source being
further constructed to generate radiation of a wavelength sensitive
to said contrast agent of known optical properties that modify said
pulses of photons while migrating in said tissue to said output
port.
41. The system of claim 40 wherein said contrast agent is
preferentially absorbed in an abnormal tissue.
42. The system of claim 34 or 35 further including an exogenous
contrast agent that includes a fluorescing material when
irradiated, said light source being further constructed to generate
radiation of a wavelength that excites fluorescent radiation from
said material, and said detector being further constructed to
detect said fluorescent radiation.
43. The system of claim 42 wherein said detector further includes a
filter constructed to pass only said fluorescent radiation.
44. The system of claim 35 wherein said processor is further
constructed to compare said determined value of the scattering
coefficient to a selected value of the scattering coefficient.
45. The system of claim 34 wherein said processor is further
constructed to compare said calculated value of the absorption
coefficient to a selected value of the absorption coefficient.
Description
BACKGROUND OF THE INVENTION
The invention features a time-resolved spectroscopic method and
apparatus for breast tissue examination.
Breast cancer is among the most common and the most feared
malignancies in women. It has an unpredictable course, the
treatment is frequently physically and emotionally draining and the
risk of metastatic spread persists for many years. Due to its high
occurrence rate, routine breast cancer screening, which includes
physical examination and x-ray mammography, plays an important role
in current health care. X-ray mammography can detect over 90% of
all masses and increases the 10-year survival rate to about 95% for
patients with cancers solely detected by mammography. Although the
modern mammography uses a low-dose of x-rays, it still involves
some small risk of inducing cancers by the radiation. Other tests,
such as magnetic resonance imaging (MRI) and gadolinium enhanced
MRI, have been used successfully for detection of breast tumors and
may be used routinely for screening in the future.
After a small suspicious mass is detected in the breast
non-invasively, an excisional biopsy is usually performed to
exclude or diagnose malignancy. The biopsy specimen is removed
under local anesthesia and is used for histopathological diagnosis.
The statistics show that in about 75% of the excisional biopsies,
the biopsied tissue is diagnosed to be benign. Thus, a majority of
patients undergoes this unpleasant and costly procedure
unnecessarily. Furthermore, it has been suggested that the
excisional biopsy may cause spreading of the malignant tumor
cells.
Therefore, a non-invasive, relatively inexpensive technique that
can detect and characterize breast tumors may find its place in
today's health care, alone or in conjunction with the
above-mentioned techniques.
SUMMARY OF THE INVENTION
The invention features an system and a method for breast tissue
examination using time-resolved spectroscopy.
In general, in one aspect, the method includes the following steps.
A support that includes an input port and an output port separated
by a selected distance is positioned relative to the examined
breast. Locations of the input and output ports are selected to
examine a tissue region of the breast. Light pulses of a selected
wavelength and duration less than a nanosecond are introduced into
the breast tissue at the input port and detected over time at the
detection port. Signals corresponding to photons of detected
modified pulses are accumulated over the arrival time of detected
photons. Values of a scattering coefficient or an absorption
coefficient of the examined breast tissue are calculated based on
the shape of the modified pulses. The examined breast tissue is
characterized based on the values of the scattering coefficient or
the absorption coefficient.
In general, in another aspect, the method includes the following
steps. A support that includes an input port and an output port
separated by a selected distance is positioned relative to the
examined breast. Locations of the input and output ports are
selected to examine a tissue region of the breast. Light pulses of
a selected wavelength and duration less than a nanosecond are
introduced into the breast tissue at the input port and detected
over time at the detection port. Signals corresponding to photons
of detected modified pulses are integrated over at least two
selected time intervals separately spaced over the arrival time of
the modified pulses. A value of an absorption coefficient of the
examined breast tissue is calculated based on the shape of the
modified pulses. The examined breast tissue is characterized based
on the value of the absorption coefficient.
In this aspect, the method may include further steps. The detected
photons are integrated over other selected time intervals
separately spaced over the arrival time of the modified pulses.
Time dependence of the light intensity is determined based on the
number of photons integrated over each time interval, and a value
of a scattering coefficient of the examined breast tissue is
determined. The examined breast tissue is characterized based on
the value of the scattering coefficient.
Preferred methods use the above-described steps and additional
steps as follows.
The input port and the output port are moved to a different
location to examine another tissue region of the breast. Values of
the scattering coefficient or absorption coefficient are again
determined by repeating the above-described steps for the newly
selected tissue region. The tissue region is characterized using
the additional values of the scattering coefficient or the
absorption coefficient.
The above-described steps are performed over several tissue regions
to examine the entire breast.
The characterizing step includes comparing the calculated values of
the scattering or absorption coefficient with selected values of
scattering or absorption coefficient, respectively.
The selected values of the scattering and absorption coefficient
correspond to normal breast tissue, normal contralateral breast
tissue or series of homogenous breast tumors.
The characterizing step includes comparing the calculated values of
the scattering coefficient or the absorption coefficient with
selected values of the scattering coefficient or the absorption
coefficient, respectively.
If the above-recited characterizing step reveals that the examined
tissue includes abnormal tissue the following steps are performed.
Other locations of the input port and the output port are selected
to define a new tissue region proximate to the region having
abnormal tissue. The values of the scattering coefficient or the
absorption coefficient of the newly selected tissue region are
determined by applying the corresponding above recited steps.
Abnormal breast tissue is localized by comparing values of the
scattering coefficient or the absorption coefficient of different
selected tissue regions. The type of the abnormal tissue may be
determined by comparing values of the scattering coefficient or the
absorption coefficient of the localized tissue to values of the
scattering coefficient or the absorption coefficient corresponding
to selected tissue masses.
The tissue masses include one of the following: carcinoma,
fibroadenoma or fibrocystic tissue.
The size and location of the abnormal tissue region is
determined.
If the above-recited characterizing step reveals that the examined
tissue includes abnormal tissue, further the following steps are
performed. A contrast agent exhibiting known optical properties at
the selected wavelength is injected into the blood stream of the
subject. Other locations of the input port and the output port are
selected to define a new tissue region proximate to the region
having abnormal tissue. The values of the scattering coefficient or
the absorption coefficient of the newly selected tissue region are
determined. The abnormal breast tissue is localized by comparing
values of the scattering coefficient or the absorption coefficient
of different selected tissue regions. The type of the abnormal
tissue may be determined by comparing values of the scattering
coefficient or the absorption coefficient of the localized tissue
to values of the scattering coefficient or the absorption
coefficient corresponding to selected tissue masses comprising the
contrast agent.
If the above-recited characterizing step reveals that the examined
tissue, includes abnormal tissue further the following steps are
performed. A contrast agent exhibiting known optical properties at
the selected wavelength is injected into the abnormal tissue. Other
locations of the input port and the output port is selected. The
values of the scattering coefficient or the absorption coefficient
of the newly selected tissue region are determined. The abnormal
breast tissue is localized by comparing values of the scattering
coefficient or the absorption coefficient of different selected
tissue regions.
The type of the abnormal tissue may be determined by comparing
values of the scattering coefficient or the absorption coefficient
of the localized tissue to values of the scattering coefficient or
the absorption coefficient corresponding to selected tissue masses
comprising the contrast agent.
The contrast agent is a fluorescing material or absorbing material.
The contrast agent is preferentially absorbed by the tissue
mass.
The above described steps are performed in conjunction with x-ray
mammography, MRI mammography or a needle localization
procedure.
In another aspect, the invention features a system for performing
the above-described method.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 depicts diagrammatically a time-resolved spectroscopic
system for breast tissue examination.
FIGS. 1A, 1B, 1C and 1D depict different embodiments of an optical
fiber support for breast tissue examination.
FIG. 2 depicts diagrammatically a single photon counting TRS
apparatus arranged for breast tissue examination.
FIG. 3 depicts diagrammatically a TRS boxcar apparatus arranged for
breast tissue examination.
FIG. 3A shows a timing diagram of the apparatus of FIG. 3.
FIG. 3B shows a typical time resolved spectrum collected by the
apparatus of FIG. 3.
FIG. 4 depicts diagrammatically examination of breast tissue using
a fluorescing contrast agent.
FIGS. 4A and 4B depict diagrammatically examination of breast
tissue using MRI and time-resolved spectroscopy.
FIGS. 5A, 5B, 5C, 5D, 5E and 5F display values of the absorption
coefficient and the scattering coefficient of normal breast tissue
measured at different locations of the right breast and of the left
breast.
FIGS. 6A and 6B display values of the absorption coefficient and
the scattering coefficient, respectively, of normal breast tissue
for women of different ethnic background.
FIG. 7 is a block diagram of a multiple gate integrator TRS pulse
system in accordance with another embodiment of the present
invention.
FIGS. 7A and 7B show a typical time resolved spectrum and a timing
diagram for the system of FIG. 7, respectively.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIG. 1 depicts a breast tissue examination system 4 placed on a
human breast 5 for breast tissue examination. The system includes
an optical fiber support 8 with multiple input ports 14 and
multiple output ports 16. Support 8 is placed around breast 5 so
that input ports 14 and output ports 16 define irradiation
locations and detection locations on the skin of breast 5,
respectively. Connected to selected input and output ports are
optical fibers 15 and 17, respectively. System 4 uses a TRS device
20 that is either a single photon tissue resolved apparatus 20A or
a time resolved apparatus 20B using boxcar type integration shown
in FIGS. 2 and 3, respectively.
Referring also to FIGS. 1A, 1B, 1C and 1D, system 4 uses different
types of the optical fiber supports designed to introduce and
detect photons at selected locations and thus shape the optical
field. The optical fiber supports are made of flexible or rigid
materials and are shaped to accommodate breasts of different
volumes. Furthermore, the inside surface of the supports may
include material of known scattering and absorptive properties. The
material is selected to either return back to the breast tissue
photons escaping through the skin (i.e., a low absorber and high
scatterer) or provide additional paths for the escaping photons to
the detector (i.e., the material has substantially the same optical
properties as normal breast tissue). The supports are designed for
use with a time-resolved spectrophotometer (TRS) alone or in
conjunction with x-ray mammography, MRI or a needle localization
procedure. Specifically, fiberoptic support 9 shown in FIG. 1A
includes three sets of the input and detection ports labeled 10a,
10b, and 10c. Sets 10a and 10c are used to measure control data and
set 10b is used to examine a suspected mass 7. Furthermore, support
9 enables precise characterization of the distances between the
three sets, between input ports 14 and detection ports 16 (.rho.)
and from the chest wall 6 to each set (d.sub.n). Supports 11 and
12, shown in FIGS. 1B, 1C and 1D, are used with x-ray mammography
and needle localization procedure, respectively, and their
functions are described below.
Referring to FIG. 2, a dual wavelength, time correlated single
photon counting TRS apparatus 20A is connected to support 13
positioned on breast 5. Pulsed laser diodes 32 and 34 (model PLP-10
made by Hamamatsu, Japan), are driven by a 5 mW pulser 36 connected
to a 100 MHz pulse generator 37, and generate light pulses on the
order of 500 psec or less. The light from laser diodes 32 and 34 is
electro-mechanically time shared using a 60 Hz vibrating mirror 33
and is coupled to one end of optical fiber 15. Optical fiber 15,
which has about 200 .mu.m diameter, alternatively conducts pulses
of 754 nm and 810 nm light to input port 14. The introduced photons
migrate in the examined breast tissue and some of them arrive at
output port 16. Optical fiber 17 collects photons of the modified
pulses from an area of about 10 mm.sup.2 and transmits them to a
PMT detector 40.
The output of PMT 40 is connected to a wide band amplifier 42 with
appropriate roll-off to give good pulse shape and optimal signal to
noise ratio. Output signals from amplifier 42 are sent to a
high/low level discriminator 44, which is a pulse amplitude
discriminator with the threshold for pulse acceptance set to a
constant fraction of the peak amplitude of the pulse. Next, the
discriminator pulses are sent to a time-to-amplitude convertor
(TAC) 46. TAC 46 produces an output pulse with an amplitude
proportional to the time difference between the start and stop
pulses received from pulser 36. The TAC pulses (47) are routed by a
switch 48 to either a multichannel analyzer (MCA) 50 or an MCA 52.
Switch 48 operates at 60 Hz and is synchronized with mirror 33. The
photon emission, detection cycle is repeated at a frequency on the
order of 10 MHz. Each MCA collects only a single photon for each
light pulse introduced to the tissue. Each MCA acquires and sums
photons of only one designated wavelength and stores the
corresponding pulse of a shape that depends on properties of the
examined tissue. The pulses are preferably accumulated over about 2
to 3 minutes so that at least 10.sup.5 counts are collected at the
maximum of the pulse shape. The detected pulse shape is analyzed by
a computer 56. Computer 56 is connected to pulse generator 37 and
MCAs 50 and 52 via an interface module 54 and is adapted to control
the entire operation of the system.
Alternatively, TRS apparatus 20 represents a boxcar TRS apparatus
20B, as shown in FIG. 3. A pulsed laser diode 60 is driven by a 5
mW pulser 62 connected to a 100 MHz pulse generator 64. Laser diode
60 generates a train of 100 ps light pulses of 754 nm wavelength
coupled to optical input fiber 15. The light pulses are introduced
to breast tissue at input port 14. The introduced photons migrate
in the examined tissue and a portion of them arrives at an output
port 16. In the migration process, the input pulse has been
modified by the scattering and absorptive properties of the
examined tissue. Photons arriving at detection port 16 are
transmitted by optical fiber 17 to a detector 66, (for example,
Hamamatsu photomultipliers R928, R1517, MCP R1712, R1892).
The output of detector 66 is amplified in a wide band
preamplifier/impedance changer 67 and coupled to a boxcar
integrator 68. Integrator 68 activated by a pulse gate 73 collects
all arriving photons over a predetermined time interval 75, as
shown in FIG. 3A. The integrator output (78) is sent to computer
interface module 80 and computer 82. Computer 82 stores the total
number of counts detected during the collection interval of
integrator 68.
Integrator 68 includes a trigger 70, which is triggered by a signal
63 from pulser 62. Trigger 70 activates a delay gate 72 which, in
turn, starts counting of all detected photons during the time
interval specified by a gate width circuit 74. Output from a gate
width normalizer 76 is an analog signal or a digital signal
representing all photons that arrived at detection port 16 during
the preselected gate width interval (75). A suitable integrator is
a boxcar SR 250 manufactured by Stanford Research Systems.
Depending on the application, computer 82 sets the delay time (71)
of delay gate 72 and the gate width time (75) of gate width circuit
74. Gate width normalizer 76 adjusts the width of the integration
time depending on the detected signal level. The gate width may be
increased logarithmically for signals at t>>t.sub.max,
wherein the detected number of photons decreases exponentially;
this increases the signal-to-noise ratio. Furthermore, computer 82
can scan the integration gate widths over the whole time profile of
the detected pulse. By scanning the delay times (71) and
appropriately adjusting the gate widths (75), the computer collects
data corresponding to the entire detected pulse. Subsequently,
computer 82 calculates the shape (85) of the detected pulse and
stores the time dependent light intensity profile I(t).
The pulse shape, I(t), detected either by apparatus 20A or
apparatus 20B possesses information about the scattering and
absorptive properties of the examined breast tissue and is used to
determine the scattering and absorption coefficients. Referring to
FIG. 3B, a test measurement was performed on apparatus 20A and
found that due to a somewhat slow response time, the detector
broadens the reflectance profile, as seen on spectrum 86. Thus the
experimental spectra (87) are deconvoluted to separate the
instrumental response from the profile dispersion due to the
diffusion. The deconvolution yields about 6% increase in the value
of .mu..sub.a and about 23% decrease in the value of
.mu..sub.s.
The examined tissue region is defined by the distribution of photon
pathlengths forming an optical field in the tissue. The size and
shape of the optical field is a function of the input-output port
separation (.rho.) as well as the optical properties of the tissue
(i.e., absorption coefficient, .mu..sub.a, scattering coefficient,
.mu..sub.s, and the mean cosine of anisotropic scattering, g). The
general diffusion equation is used to describe the photon migration
in tissue, as analyzed by E. M. Sevick, B. Chance, J. Leigh, S.
Nioka, and M. Maris in Analytical Biochemistry 195, 330 (1991),
which is incorporated by reference as if fully set forth herein.
The diffusion equation is solved for the intensity of detected
light in the reflectance geometry, R(.rho.,t), or the transmittance
geometry T(.rho.,d,t). In the reflectance geometry, in a
semi-infinite media with the separation of the input and output
ports on the order of centimeters, the absorption coefficient is a
function of the reflectance spectrum as follows: ##EQU1## For
t.fwdarw..infin. the absorption coefficient .mu..sub.a is
determined as follows: ##EQU2## wherein .rho. is the separation
between input and detection ports and c is speed of light in the
medium. However, it is difficult to measure the at
t>>t.sub.max because in this region the data show substantial
noise. Thus, to measure .mu..sub.a at t>>t.sub.max, requires
determination of the pulse shape at a high number of counts.
If the approximation of infinite time is not valid, Eq. 1 can be
rewritten to obtain .mu..sub.a as follows: ##EQU3## The value for D
can either be the average value obtained from numerical simulations
or a value specific to the type of tissue being measured.
The effective scattering coefficient (1-g).multidot..mu..sub.s is
determined as follows: ##EQU4## wherein t.sub.max is the delay time
at which the detected reflectance time profile
(R(.rho.,t).ident.I(t)) reaches maximum. After detecting the pulse
shape corresponding to the examined tissue the computer calculates
the absorption coefficient (.mu..sub.a), and the scattering
coefficient (.mu..sub.s). The absorption coefficient is quantified
by evaluating the decaying slope of the detected pulse, using Eqs.
2 or 3. The effective scattering coefficient,
(1-g).multidot..mu..sub.s, is determined from Eq. 4.
The breast screening procedure starts by selecting a support with
appropriate arrangement of input ports 14 and output ports 16. The
absorptive and scattering properties of the tissue are measured for
one set of ports and then the optical field is transferred by using
another set of ports. The entire breast is examined by selecting
sequentially different ports. In the reflection geometry, the
optical field can be represented by a three dimensional,
"banana-shaped" distribution pattern or, in the transmission
geometry, a "cigar-shaped" distribution pattern. In the
"banana-shaped" pattern, the shallow boundary is due to the escape
of photons that reach the air-scatterer interface while the deeper
boundary is due to attenuation of long path photons by the
absorbers. The penetration depth of the photons is about one half
of the port separation (.rho.). During the screening procedure, the
computer calculates .mu..sub.a and .mu..sub.s for the entire breast
and compares the measured values with threshold values of
.mu..sub.a and .mu..sub.s of normal tissue or series of .mu..sub.a
and .mu..sub.s values of different homogeneous tumor types. As is
shown in FIGS. 5A through 5F, from one person to another there is
some variation in .mu..sub.a and .mu..sub.s for normal tissue, but
only a very small variation between the left breast and the right
breast of the same person. Cancerous tissue, which is usually
highly perfused, exhibits higher values of .mu..sub.a and
.mu..sub.s than fibrous tissue. Normal tissue, which has a
relatively high amount of fat, exhibits the lowest values of
.mu..sub.a and .mu..sub.s.
Alternatively, instead of calculating .mu..sub.a and .mu..sub.s,
the system can calculate an average pathlength of the migrating
photons. From the detected and deconvoluted photon intensity
profile, R(t), a mean pathlength of the distribution of pathlengths
<L> is determined as follows: ##EQU5## wherein c is the speed
of light in vacuum and n.apprxeq.1.36 is the average refractive
index of tissue.
If a breast tumor is outside of the optical field, it does not
alter the banana-shaped distribution of pathlengths. As the optical
field is moved closer to the breast tumor, which is a strongly
absorbing mass, the photons that have migrated the farthest
distance from the input and detection ports are eliminated by the
absorption process. Since photons with the longest pathlengths are
absorbed by the mass, the system detects reduction in the average
pathlength. When the optical field is moved even closer to the
mass, some of the detected photons now migrate around the mass
without being absorbed; this is detected as lengthening of the
distribution of pathlengths. Thus, the average pathlength
measurement can reveal location of the breast mass.
In the screening process, the breast tissue is characterized by
several tissue variables which may be used alone or in combination.
TRS device 20 measures the absorption coefficient, the scattering
coefficient, the blood volume or tissue oxygenation using one or
more selected wavelengths of the laser. The wavelengths are
sensitive to naturally occurring pigments or contrast agents that
may be preferentially absorbed by the diseased tissue. Suitable
naturally occurring pigments are, for example, hemoglobin (Hb) or
oxyhemoglobin (HbO.sub.2) sensitive to 754 nm and 816 nm,
respectively.
Alternatively, suitable color dyes, such as cardio-green or
indocyinin-green, may be injected to the blood system alone or
bound to a vehicle such as a gadolinium contrast agent, which is
preferentially absorbed by tumors in the first five to ten minutes.
An appropriate wavelength is selected for the color dye, for
example, cardio-green exhibits maximum absorption at 805 nm.
The computer can create "maps" of the breast by mapping the spacial
variation of the measured values for .mu..sub.a, .mu..sub.s, blood
volume or hemoglobin saturation. The resolution is enhanced when
several tissue variables are mapped. The blood volume is measured
using a pair of contrabestic wavelengths (e.g., 754 nm and 816 nm)
or the isobestic wavelength (i.e., 805 nm). The hemoglobin
saturation (Y) is measured at two wavelengths (e.g., 754 nm and 816
nm) and is calculated by taking the ratio of absorption
coefficients at these wavelengths and then using the following
equation: ##EQU6## wherein the coefficients are determined from the
extinction values of hemoglobin at 754 nm and 816 nm that are
.epsilon..sub.Hb =0.38 cm.sup.-1 mM.sup.-1 .epsilon..sub.Hb =0.18
cm.sup.-1 mM.sup.-1, respectively, and the difference in extinction
coefficients between oxyhemoglobin and hemoglobin that are
.increment..epsilon..sub.Hb0-Hb =0.025 cm.sup.-1 mM.sup.-1 and
.increment..epsilon..sub.Hb0-Hb =0.03 cm.sup.-1 mM.sup.-1,
respectively.
In another preferred embodiment, TRS apparatus 20 is used in
combination with x-ray mammography. The combined procedure is
performed if a suspected mass is detected by the above-described
optical method, x-ray mammography or another screening method.
Referring to FIG. 1B, breast 5 is compressed in either a horizontal
or vertical position between an x-ray film case 90 with the x-ray
film and a support 11 with input ports and output ports located on
a grid. An x-ray mammogram is taken to determine location of
suspected mass 7 relative to the grid. Suitable input port 14 and
output port 16 are selected so that the introduced optical field 92
encompasses mass 7. Then, TRS apparatus 20A or 20B is used to
measure .mu..sub.a, .mu..sub.s, the blood volume or oxygen
concentration of the examined tissue using the above-described
techniques. The measured values are again compared to the values
corresponding to normal tissue or different types of diseased
tissue to characterize the mass. If an unequivocal result is
obtained, an exploratory excisional biopsy is not needed.
In another preferred embodiment, TRS apparatus 20 is used in
combination with the needle localization procedure. The needle
localization procedure locates the mass that is then examined by
system 4. Furthermore, a needle used in the needle localization
procedure may introduce an optical fiber directly to mass 7.
Referring to FIGS. 1C and 1D, breast 5 is compressed between x-ray
film case 90 and a support 12 with input ports and output ports
located on a grid and a centrally located opening for a needle 94
or a needle 98. One or more x-ray mammograms are taken to determine
the location of suspected mass 7 relative to the grid and to the
needle opening. The needle is inserted into the breast and the
needle tip is positioned in the center of mass 7. Additional x-ray
mammograms may be taken to verify or adjust the position of the
needle.
As shown in FIG. 1C, if the needle is used only to localize mass 7,
input port 14 and output port 16 are selected so that their
separation is equal or larger than two times the depth of mass 7.
This separation assures that the introduced optical field 96
encompasses mass 7. After needle 94 is positioned, a tiny wire is
inserted into the mass and left there for marking purposes. TRS
apparatus 20 measures .mu..sub.a, .mu..sub.s, blood volume or
oxygen concentration of the examined tissue using the
above-described techniques. The measured values are again compared
to the values of normal tissue and different types of diseased to
characterize tissue, and the tissue of mass 7.
As shown in FIG. 1D, needle 98 positions an end 99 of optical input
fiber 15 directly inside mass 7. Here, the optical fiber with a
diameter of about 100 .mu.m or less is threaded inside needle 98
and end 99 is slightly extended from the needle so that the
introduced photons are directly coupled to mass 7. The location of
detection port 16 defines optical field 100. In this arrangement,
all detected photons migrate in the targeted tissue; this increases
the relative amount of the targeted tissue being examined and thus
increases the resolution of the system. To compare tissue of mass 7
with normal tissue, the same geometry of the input port and the
detection port is used to measure the optical properties of the
contralateral breast. Alternatively, in the same breast, needle 98
is moved outside of mass 7 so that the positions of the optical
fiber end 99 and detection port 16 define an optical field
completely removed from mass 7. To characterize the mass, the
values of .mu..sub.a and .mu..sub.s measured for mass 7 are
compared either to the values of normal tissue measured in the same
arrangement or to values of different types of diseased tissue.
In another embodiment, the detection contrast is enhanced using
fluorescing contrast agents. A tumor is permeated with a
fluorescing contrast agent that has a decay time of less than 1
nsec, and the labeled tumor is then again examined using TRS device
20. Suitable agents emit fluorescing radiation in the range of 800
nm to 1000 nm, for example, carbocyanene dyes or porphorin
compounds.
Referring to FIG. 4, the fluorescing contrast agent is injected to
the blood system alone or bound to a vehicle, such as a gadolinium
contrast agent, which is initially preferentially absorbed by a
breast tumor. Alternatively, the fluorescing agent is injected
directly into the tumor. TRS device 20 generates 150 psec light
pulses introduced into breast 5 at input port 14. The introduced
photons of selected excitation wavelength reach tumor 7 and excite
a fluorescing radiation 110, which propagates in all directions
from tumor 7. The photons of fluorescing radiation 110 migrate in
the examined breast tissue and some of them arrive at output port
16. Output port 16 has an interference filter that passes only
photons at the wavelength of fluorescing radiation 110. Optical
fiber 17 collects the transmitted photons, which are delivered to
the PMT detector. System 4 may detect fluorescing radiation 110 at
several output ports at the same time or move the ports to
different positions on the fiber optic support.
TRS device 20 detects the pulses of fluorescing radiation 110; the
shape of these pulses depends on the decay time of the fluorescing
agent and optical properties of both the tumor tissue and the
normal breast tissue.
In another embodiment, referring to FIGS. 4A and 4B, TRS apparatus
20 is used in combination with MRI. MRI examines the breast with or
without using a rare earth contrast agent. A network of surface
coils 112 is cooperatively arranged with a fiberoptic support 114,
which is constructed for use with MRI. The network of coils 112 and
support 114 are appropriately located around the examined breast.
At the same time as the MRI data are collected, TRS apparatus 20
collects the optical data. If an abnormal mass is detected, MRI
identifies the size and location of the mass. The optical data are
then used to characterize the mass. Optical contrast agents may be
used alone or in combination with the rare earth contrast agents,
as described above.
EXPERIMENTS
Preliminary experiments were conducted under a pre-approved
protocol and after receiving informed consent of women with normal
breast tissue and of women having a mass detected in their
breast.
The examination of normal breast tissue was performed at several
different locations of the right and left breast of the same woman.
Referring to FIGS. 2 and 3, letters RR, LR, LR and LL denote the
right and left breast and the right and left breast side where the
input and detection ports were located, respectively. FIGS. 5A and
5B summarize the absorption coefficient (.mu..sub.a) and the
scattering coefficient (.mu..sub.s '=(1-g).multidot..mu..sub.s),
respectively, measured on the right and left breast at a separation
.rho.=6 cm. The values of .mu..sub.a and .mu..sub.s ' for the right
breast are identical to the values for the left breast within the
measurement error. FIGS. 5C and 5D summarize .mu..sub.a, .mu..sub.s
', respectively, for the tissue on the left side and the right side
of each breast, and FIGS. 5E and 5F summarize .mu..sub.a,
.mu..sub.s ', respectively, for the tissue located at different
distances from the chest wall. The data shown in FIGS. 5A through
5F confirm that there is no significant difference in the optical
properties measured over the entire breast.
The examination of normal breast tissue also measured differences
in the optical properties corresponding to the volume of the
breast, type of the breast tissue, the age of the woman and ethnic
background. Based on the decreasing X-ray background absorption,
the breast tissue was categorized as "dense" "fatty" or a "mixture"
of the two tissue types. The values of .mu..sub.a and .mu..sub.s '
of "fatty" tissue are lower than for "dense" tissue, which has a
higher fibrous content. Since the shape of the breast varies, it
was difficult to categorize precisely the breast volume. For the
volume measurement, the breast was stabilized on a plate and the
length was measured from the chest to the end of the breast. The
width and the thickness were measured at approximately 1 cm from
the chest. Tissue of a large volume breast exhibits lower values of
.mu..sub.a and .mu..sub.s ' than that of a small volume breast. The
same trend is observed for women above the age 50 when compared to
women below 50. FIGS. 6A and 6B display values of .mu..sub.a and
.mu..sub.s ', respectively for Caucasians and African-Americans.
Normal breast tissue of Caucasians and African-Americans exhibits
substantially the same optical properties except for the values of
.mu..sub.s ' measured at the 4 cm separation. Since the skin forms
a higher relative percentage of the examined tissue at a smaller
separation of the input and output ports, the lower values of
.mu..sub.s ' may be due to a lower scattering coefficient of the
skin with more pigment.
In all measurements, a smaller separation of the input and output
ports yielded larger values of .mu..sub.a and .mu..sub.s ' than a
larger separation of the ports. This differences can be explained
by violation of the semi-infinite boundary conditions at the
smaller separations, i.e., a larger escape of photons through the
tissue surface before they are collected by optical fiber 17.
Furthermore, this dependence exists since the slope of the photon
decay was measured not sufficiently far from the peak of the
reflectance data as expressed in Eqs. 1, 2 and 3. This problem
arises due to a low photon count of approximately 10,000 counts at
the peak. Thus the measured data have a low signal to noise ratio
and a reliable reflectance data can not be taken at
t>>t.sub.max. The corresponding error in the absorption
coefficient, E(.rho.,t) .vertline..sub.abs, is determined using Eq.
7. ##EQU7## The error of scattering coefficient,
E(.rho.,t,.mu..sub.a) .vertline..sub.sct, arises due to the error
in the absorption coefficient. The corresponding error is
determined using Eq. 8. ##EQU8## The preliminary values of
.mu..sub.a and .mu..sub.s ' corrected for the error using Eqs. 7.
and 8 are shown in Table 1.
TABLE 1 ______________________________________ .mu..sub.a Mean
.mu..sub.s Separation Mean Error Mean t.sub.max Error (cm)
.mu..sub.a Adjusted .mu..sub.s (ns) Adjusted
______________________________________ 4 0.029 0.020 16.2 1.55 14.1
5 0.023 0.021 11.4 1.9 10.9 6 0.019 0.022 9.5 2.3 10.1 7 0.017
0.021 7.9 2.7 8.7 ______________________________________
The corrected values of mean .mu..sub.a for different separations,
.rho., are substantially the same, but the corrected values of mean
.mu..sub.s still are .rho. dependent although their spread is
reduced considerably.
The examination of a breast with abnormal tissue was performed
substantially the same way as the above-described examination of
normal breast tissue. The breast tissue was first characterized by
x-ray mammography and the size and location of a mass was
determined. The examined breast was compressed between x-ray film
case 90 and a support 12, as shown in FIG. 1C. Input port 14 and
output port 16 were selected so that mass 7 was located in optical
field 96.
The values of .mu..sub.a and .mu..sub.s ' measured around tumor 7
(using input output port set 10b of FIG. 1A) were compared to
control data measured on the same breast (using input output port
sets 10a and 10c of FIG. 1A). The measured data were also
correlated with pathology information on abnormalities in the
examined breasts. The abnormalities were divided into the following
three categories: fibrocystic, Fibroadenoma, and Carcinoma.
Furthermore, these three categories are subdivided according to the
size of the tumors as follows: smaller in diameter than 1 cm, and
equal or larger in the diameter than 1 cm. Preliminary data
measured on over fifty patients show an increase in the values of
both .mu..sub.a and .mu..sub.s ' when compared with normal tissue
but statistical significance has not been demonstrated.
Referring to FIG. 7, alternatively, multiple (at least three),
parallel integrators are used in a faster and more efficient
system. This system 20B may be used to determine the whole profile
of the detected pulse (189) shown in FIG. 7A, by appropriately
selecting the delay gates and the gate widths.
Pulse generator 152 connected to a pulser 154 drive alternately
laser 156 and 157. The alternate coupling is provided by a switcher
153 that operates at frequencies on the order of 10.sup.7 Hz.
Pulses of light of wavelength in the visible or infra-red range and
duration 10.sup.-9 to 10.sup.-10 second are alternately coupled to
the subject via optical fibers 198 or other light guide. The light
pulses are modified by tissue of subject 150 positioned between the
input port of fiber 198 and the detection port of fiber 100. The
modified pulses are detected by detector 102 and the detected
signal is amplified by preamplifier 104. Integrators 180, 182, and
184 collect data during selected gate width intervals, as shown on
the timing diagram of FIG. 7B. Trigger 155 correlated with the
input pulse, triggers delay gates 1, 2, and 3 (shown in FIG. 7B)
that are set to have selected delay timer. Each delay gate then
triggers its corresponding integrator that collects all photons
that arrive at the detector during the delay width time. Each
integrator collects photons arriving at the detection port during
its integration time defined by the gate width. This configuration
can achieve a repetition rate of at least 10 kHz.
The gate arrangement of FIGS. 7A and 7B uses gates 191 and 195 to
detect the decay slope of the signal while the third gate 199 may
be used to determine the background signal. Outputs 192 and 196 of
integrators 180 and 182 are used to calculate the slope.
To obtain approximately equal signal-to-noise ratios in the
individual integrators, the length of the time windows is tailored
to an exponential decay of the signal intensity with a logarithmic
increase in the gate width with delay time.
Referring to FIGS. 7A and 7B, by scanning the delay gates (190,
194, and 198) and appropriately adjusting the gate widths, the
system collects data corresponding to the entire detected pulse;
subsequently, the shape (189) of the detected pulse is then
calculated, i.e., time dependent light intensity profile I(t) is
determined. The detected pulse shape, I(t), possesses information
about the scattering and absorption properties of the examined
tissue, which are closely related to the distribution of photon
pathlengths in the tissue. The optical field is a function of the
input-output port separation (.rho.) as well as the optical
properties of the tissue (absorption coefficient, .mu..sub.a,
scattering coefficient, .mu..sub.s, and the mean cosine of
anisotropic scattering, g). The general diffusion equation is used
to describe the photon migration in tissue, as described by E. M.
Sevick, B. Chance, J. Leigh, S. Nioka, and M. Marie in Analytical
Biochemistry 195, 330 (1991) which is incorporated by reference as
if fully set forth herein.
Other embodiments are within the following claims:
* * * * *